A high resolution imaging method for joint soft tissues would aid in the diagnosis and treatment of Rheumatoid Arthritis (RA) and Osteoarthritis (OA), by helping detect their destructive effects well before they are evident in conventional radiography. These diseases affect a significant fraction of the world population and attack most of the joints in the body, including large joints such as the knee, hip, or shoulder. None of the current imaging modalities can simultaneously provide good soft tissue contrast and spatial resolution for large joints. MRI and ultrasound offer good soft tissue contrast, but their spatial resolution is limited. Conventional absorption based X-ray imaging provides better spatial resolution, but has poor soft tissue contrast. In recent years a new X-ray imaging modality named differential phase contrast (DPC) and based on X- ray refraction instead of absorption has been developed at synchrotron accelerators. The method has a strong contrast enhancing effect for joint tissue boundaries and for micro-structured tissues such as cartilage, tendon, ligament or muscle, enabling in the synchrotron experiments to image with high resolution soft tissues in the human knee, ankle or hand joints. In addition, since it uses the transmitted radiation, DPC can work at lower dose than conventional X-ray imaging. The goal of the present 2-year proposal is to develop and test in the laboratory a system that will enable DPC imaging of large joints using conventional X-ray tubes. The system will be based on a novel type of X-ray interferometer having micro-periodic mirrors at grazing incidence and phase gratings as main optical elements, and will work at high enough X-ray energy to penetrate large joints. Our numerical study shows that such a system will enable imaging with high resolution soft tissues in large joints such as the cartilage in the knee. The micro-periodic mirrors will be made in a simple and inexpensive manner by lithographically patterning a high-Z film on a low-Z substrate. The mirror based system is suited for line scan phase-contrast imaging, in which the detector is a linear array and the interferometer or the object is spatially scanned. The longer term goal of our research is to develop a system that will enable clinical X-ray DPC imaging of large joints. This system will be made available to physicians at JHU Rheumatology and Radiology for first clinical studies on human patients. If successful, such systems may enable an improved diagnosis of RA and OA disease and better evaluation of new therapies, at radiation dose and costs comparable to conventional X- ray imaging. The R21 research will prepare the grounds for the clinical prototype development, by fabricating and testing mirror optics, by demonstrating the DPC system for high energy, and by studying and optimizing DPC line scan imaging and tomography of large joints, on phantoms and on ex-vivo animal samples. PUBLIC HEALTH RELEVANCE: A novel type of X-ray imaging system is proposed that will enable high resolution imaging of soft tissues inside large body joints for an improved diagnosis and treatment monitoring in Rheumatoid Arthritis (RA) and Osteoarthritis (OA) disease. The instrument is based on an X- ray mirror interferometer which will enable line-scan imaging of joint soft tissues with much better resolution than possible with any current imaging modality, at radiation dose no higher than in conventional X-ray radiography. This in turn can help detect the destructive effects of RA and OA disease well before they are evident in conventional radiography, as well as improve the evaluation of new treatments.